Adhesion of Staphylococcus aureus to implanted cardiovascular device surfaces involve a binding of bacterial receptors to host proteins adsorbed on the surface of the biomaterial. Five matrix proteins - fibronectin, fibrinogen, thrombospondin, vitronectin and collagen have been shown to serve as substrates for the adhesion of S. aureus in vitro. We propose to isolate and biochemically characterize the bacterial receptor proteins focusing on determining the structure of the ligand binding sites. The bacterial recognition sites in the ligand proteins will also be defined. The information generated from these studies would help us design inhibitor peptides which will be tested for their ability to interfere with the binding of host protein ligands to bacterial cells. In future studies, the therapeutical effects of these inhibitors will be evaluated. In initial experiments, the profiles of matrix protein receptors will be determined on collections of skin isolates and clinical isolates obtained from different kinds of implanted cardiovascular devices. An increased frequency of a particular receptor in certain types of infections would indicate an importance of this receptor as a virulence factor. These data will help us prioritize the planned biochemical studies. To determine the role of biomaterial surface composition, topography and biological interface stability, we will characterize the structural and chemical properties of new and post infected device surfaces. The results from these experiments will be a) correlated with device susceptibility to infection, b) correlated with receptor profiles of isolated strains and c) used to design substrates for clinically relevant in vitro adhesion experiments.